Oral Inflammation and Human Papilloma Virus Association among Hispanics.

Background: Identifying factors related to persistent human papillomavirus (HPV) infection is essential to reduce the incidence of HPV-related cancers. Objective: To evaluate whether gingival/periodontal inflammation is associated with oral HPV infection. Methods: This cross-sectional study (n = 740) uses data from the follow-up visit of the San Juan Overweight Adults Longitudinal Study, which recruited overweight/obese adults aged 40-65 from Puerto Rico. Participants completed a dental examination and two interviews (face-to-face/ACASI) and provided oral rinse samples for HPV detection. Oral inflammation was assessed using two definitions: (1) the number of sites with bleeding on probing (BOP), and (2) the number of teeth with probing pocket depths (PPD) ≥ 4 mm and BOP. Multivariate logistic regression was used to assess the association between oral inflammation and oral HPV. Results: Nearly three-quarters (72%) of participants were female, and 68% had 50 years or older. Participants with HPV had a higher mean number of sites with BOP (15.5 vs. 10.1) and teeth with PPD ≥ 4 mm and BOP (8.5 vs. 3.2) than participants without HPV (p < 0.05). After adjusting for sex, age, income, and the number of oral sex partners, the odds of having an oral HPV infection increased by 3% (95% confidence interval (CI): 1.00-1.06) for any additional sites with BOP and 5% (95% CI: 1.02-1.09) for any other teeth with PPD ≥ 4 mm and BOP. Conclusions: We found that oral inflammation was associated with oral HPV infection among adults in Puerto Rico. Future studies need to further investigate the underlying mechanisms.

Periodontal Disease, Local and Systemic Inflammation in Puerto Ricans with Type 2 Diabetes Mellitus.

Periodontal disease (PD) is prevalent in type 2 diabetic condition (T2DM). OBJECTIVES: We assessed the associations between serum or gingival crevicular fluid (GCF) endothelial and inflammatory mediators and chronic PD among T2DM Hispanic adults. METHODS: We enrolled 248 Puerto Rican residents with T2DM aged 40-65 years. The exposures included serum inflammatory mediators (IL-1b, IL-6, IL-10, and TNF-α), endothelial adhesion molecules, RANKL levels, and the GCF content of these analytes from a subset of 158 samples. The outcomes included the percent of sites with a probing pocket depth (PPD) ≥ 4 mm and clinical attachment loss ≥ 4 mm. Adjusted logistic regression models were fit to the categorized outcomes. RESULTS: Increased serum IL-10 (Adj. OR: 1.10, p = 0.04), sICAM-1 (Adj. OR: 1.01; p = 0.06), and elevated serum IL-1ß (Adj. OR: 1.93; p = 0.06) were statistically significant or close to being significantly associated with a percent of sites with PPD ≥ 4 mm. An increase in GCF IL-1α (Adj. OR: 1.16; p < 0.01) and IL-1ß (Adj: 2.40; p = 0.02) was associated with periodontal parameters. CONCLUSIONS: Our findings suggested that oral and systemic endothelial and inflammatory mediators are associated with periodontal clinical parameters among Hispanic adults with T2DM.

Systemic Inflammation, Endothelial Function, and Risk of Periodontitis in Overweight/Obese Adults.

The network interaction between systemic inflammatory mediators, endothelial cell adhesion function, and adiponectin as mediators of the association between metabolic diseases and periodontitis has not been evaluated. The objective of this study is to assess whether the interaction of baseline serum levels of TNF-α, hs-CRP, ICAM-1, VCAM-1, and adiponectin leads to periodontitis. Five hundred and ninety-seven overweight/obese (overweight: BMI 25 to <30 kg/m2; obese: >30 kg/m2) adults, aged 40-65 years, with complete 3-year follow-up data were included. Generalized structural equation models with negative binomial regression were used to estimate the regression coefficient (ß) for the outcome number of teeth with probing pocket depth (PPD) ≥ 4 mm and bleeding on probing (BOP) at 3-year follow-up for a 1 standard deviation unit increase (Δ = +1SD) in each biomarker. After adjusting for multiple covariates, baseline ICAM-1 and VCAM-1 had significant direct effects on increased log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 0.16; 95% CI: 0.02-0.30; ß: 0.15; 95% CI: 0.02-0.30, respectively). Baseline hs-CRP showed a significant indirect effect via ICAM-1 on the log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 4.84; 95% CI: 0.27-9.42). Thus, elevated serum ICAM-1 and VCAM-1 have a significant direct effect and increased hs-CRP has a significant indirect effect on the predicted level of periodontitis at the 3-year follow-up among overweight/obese Hispanic adults.

Diabetes self-care activities and perception and glycemic control in adult Puerto Rican residents with Type 2 Diabetes: The LLIPDS Study.

Background: Individuals with diabetes frequently have comorbid health conditions and suffer longer term complications. The control of blood glucose relies on diabetes management/self-care behaviors. Poor glycemic control, commonly encountered in underserved populations with type 2 diabetes (T2D) often results from inadequate diabetes self-care activities and/or perception. We aimed to assess the association between diabetes self-care activities/perception and glycemic control in adult Puerto Rican residents with T2D. Design and methods: We used a cross-sectional study design; our sample population was 260 individuals aged 40-65 years with T2D. We asked participants about their diabetes self-care over 8 weeks. High fasting blood glucose (≥130 mg/dL) and glycated hemoglobin (HbA1c; ≥7%) measures were defined. We estimated the strength of the following associations using logistic regression: each of three self-care activities and fasting glucose or HbA1c, adjusting for confounders. Results: Nearly 27% of the participants reported not checking their glucose levels, 7% did not take their medications as prescribed and 31% perceived their diabetes self-care as poor. Participants with less education perceived their diabetes self-care as poor more often than their counterparts (44% vs 25%; p = 0.003). Most participants had high glycemic levels (60%) or hbA1c levels (65%). Participants who perceived their diabetes self-care as poor had higher HbA1c levels than their counterparts (adj. odds ratio: 2.14, 95% CI (1.13, 4.08)). Conclusion: Poor diabetes self-care perception, possibly related to less education, likely explains poor glycemic control among adult Puerto Rican residents with T2D.

Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years.

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40-65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (ß = -1.6, p = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (ß = -1.4, p = 0.022; ß = -1.6, p = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (ß = -1.6, p = 0.038; ß = -1.9, p = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period.

Longitudinal association between adiposity and inter-arm blood pressure difference.

This is the first longitudinal study evaluating whether adiposity is associated with inter-arm blood pressure difference. We evaluated 714 overweight/obese individuals aged 40-65 years over a 3-year follow-up. Systolic and diastolic blood pressures were measured in both arms simultaneously using an automated machine. Linear regression assessed the associations of body mass index, fat %, waist, neck, thigh, and arm circumferences (cm), with absolute inter-arm differences in systolic (IAS) and diastolic (IAD) blood pressure (mm Hg). Poisson regression was used for binary outcomes (IAS and IAD ≥ 10 mm Hg). All models were adjusted for age, gender, smoking, physical activity, and HOMA-IR. Adiposity measures were associated with increased IAS and IAD (ß range: 0.09-0.20 and 0.09-0.30). Neck circumference showed the strongest association with IAS (ß = 0.20, 95% CI: 0.03, 0.37) and IAD (ß = 0.30, 95% CI: 0.12, 0.47); arm circumference showed a similar association with IAS, but lower with IAD. Highest quartiles of BMI, thigh, and arm showed significant associations with IAS (IRR: 2.21, 2.46 and 2.70). Highest quartiles of BMI, waist, neck, and arm circumferences were significantly associated with IAD (IRR: 2.38, 2.68, 4.50 and 2.24). If the associations are corroborated in other populations, adiposity may be an important modifiable risk factor for inter-arm blood pressure difference with a large potential public health impact.

Is Human Papilloma Virus Infection Linked to Periodontitis? A Narrative Review.

PURPOSE OF REVIEW: Research suggests that periodontal tissue might serve as a reservoir for oral human papillomavirus (HPV) infection, while another hypothesis is that chronic inflammation of the tissue might perpetuate an infection with oral HPV infection. In this narrative review, we summarize the evidence related to a potential association between oral HPV infection and periodontitis. RECENT FINDINGS: Twelve articles were identified, and their key findings summarized. Studies vary in sample size, study population, study design, and methods for assessment of oral HPV and periodontitis. Although results are conflicting and still inconclusive, various studies have found an association between oral HPV infection and periodontitis, which is supported by biological plausibility. SUMMARY: Future longitudinal studies should further evaluate this association, using clinical definitions of oral HPV infection and periodontitis, and focusing on high-risk populations for oral HPV infection. Studying this association is important since periodontitis might help identify at-risk individuals for oral HPV infection and potentially HPV-related oropharyngeal cancers.

Insulin resistance predicts the risk of gingival/periodontal inflammation.

OBJECTIVES: Evaluate whether insulin resistance (IR) predicts the risk of oral inflammation, assessed as the number of sites with bleeding on probing (BOP) and number of teeth with probing pocket depths (PPD) ≥ 4 mm and BOP. METHODS: Data on 870 overweight/obese diabetes free adults, aged 40-65 years from the San Juan Overweight Adults Longitudinal Study over a three-year period, was analyzed. Baseline IR, assessed using the Homeostasis Model Assessment of IR (HOMA-IR) index, was divided into tertiles. BOP was assessed at buccal and lingual sites, and PPD at six sites per tooth. Negative binomial regression was used to estimate the risk ratios (RRs) for oral inflammation adjusted for baseline age, gender, smoking status, alcohol intake, education, physical activity, waist circumference, mean plaque index, and baseline number of sites with BOP, or number of teeth with PPD≥4 mm and BOP. The potential impact of tertiles of serum TNF-α and adiponectin on the IR-oral inflammation association was also assessed in a subsample of 597 participants. RESULTS: Participants in the highest HOMA-IR tertile at baseline had significantly higher numbers of sites with BOP [RR = 1.19, 95% confidence interval (CI): 1.03-1.36] and number of teeth with PPD ≥ 4 mm and BOP (RR = 1.39, 95% CI: 1.09-1.78) at follow-up, compared with individuals in the lower two HOMA-IR tertiles. Neither TNF-α nor adiponectin confounded the associations. CONCLUSION: IR significantly predicts gingival/periodontal inflammation in this population.

Cross-sectional associations of impaired glucose metabolism measures with bleeding on probing and periodontitis.

AIM: This study assessed the associations of pre-diabetes and insulin resistance with bleeding on probing (BOP) and periodontitis among adults. MATERIALS AND METHODS: We included 1191 Hispanic adults aged 40-65 years, free of diabetes, enrolled in San Juan Overweight Adults Longitudinal Study. Pre-diabetes was defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired glycated haemoglobin. Impaired one-hour plasma glucose (1hPG) was defined as levels >155 mg/dl. Insulin resistance was defined using the study population-specific 75th percentile (HOMA-IR ≥ 3.13). High BOP was defined as percentage of teeth with bleeding ≥30%. Periodontitis was defined according to the CDC/AAP definition. RESULTS: After multivariable adjustment for age, gender, education, smoking status, alcohol consumption, physical activity, obesity, HDL-C, and plaque index, pre-diabetes with and without 1hPG, IFG, impaired 1hPG, IGT, and HOMA-IR were significantly associated with high BOP; pre-diabetes, IFG, and impaired 1hPG were significantly associated with severe periodontitis. Most of these associations remained significant when the analyses were restricted to non-smokers. CONCLUSIONS: This study suggests associations between pre-diabetes and insulin resistance with BOP and periodontitis. Given the high prevalence of impaired glucose metabolism and periodontitis, the assessment of the temporal sequence of these associations is of utmost importance.

Diabetes and increased lipid peroxidation are associated with systemic inflammation even in well-controlled patients.

BACKGROUND: The effect of the interaction between type 2 diabetes and dyslipidemia on inflammation and lipid peroxidation (LPO) has not been assessed. AIM: To investigate whether diabetes coupled with dyslipidemia alters oxidative metabolism leading to increased LPO products and inflammatory status. METHODS: 100 patients were divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetes with dyslipidemia (DM-PC/D), well-controlled diabetes with dyslipidemia (DM-WC/D), normoglycemic individuals with dyslipidemia (NG/D), and normoglycemic individuals without dyslipidemia (NG/ND). Plasma was evaluated for an LPO product (MDA), antioxidant levels and inflammatory cytokines. RESULTS: Diabetics presented significantly higher levels of LPO (p<0.05) and the DM-PC/D had higher levels of proinflammatory cytokines and MDA in the plasma in comparison with normoglycemics (p<0.05). Interestingly IL1-ß, IL-6, and TNF-α in DM-WC/D were not statistically different from those in DM-PC/D. Normoglycemic individuals with dyslipidemia presented significantly increased levels of IL-6 and TNF-α when compared to normoglycemic without dyslipidemia (p<0.05). MDA levels were also positively correlated with the presence of DM complications (r=0.42, p<0.01). CONCLUSIONS: These findings show that dyslipidemia is associated with an increased inflammatory status, even in well-controlled diabetics and in normoglycemics. Our results suggest that lipid metabolism and peroxidation are important for the development of inflammation, which is elevated in several complications associated with diabetes.

Relationship between periodontal disease and asthma among overweight/obese adults.

AIM: To assess the relationship between oral health and asthma. METHODS: Data from 1315 overweight or obese individuals, aged 40-65 years were used. Asthma was self-reported, whereas periodontitis, bleeding on probing (BOP) and plaque index were determined by clinical examinations. RESULTS: Using logistic regression adjusting for gender, smoking status, age, body mass index, family history of asthma and income level, revealed that the odds ratio (OR) of asthma for a participant with severe periodontitis was 0.44 (95% confidence interval: 0.27, 0.70) that of a participant with none/mild periodontitis. On the other hand, proportion of BOP sites and plaque index were not statistically significant. For a participant with severe periodontitis, the OR of taking asthma medication was 0.20 (95% confidence interval: 0.09, 0.43) that of a participant with none/mild periodontitis. Moreover, proportion of BOP sites was statistically associated with use of asthma medication, whereas plaque index still remained non-significant. CONCLUSION: Participants with severe periodontitis were less likely to have asthma. Stronger evidence of an inverse association was found when using asthma medication as outcome.

Lipid-lowering agents use and systemic and oral inflammation in overweight or obese adult Puerto Ricans: the San Juan Overweight Adults Longitudinal Study (SOALS).

UNLABELLED: The effects of lipid-lowering agents (LLA) on reducing systemic and oral inflammation have not been evaluated. OBJECTIVE: To assess the association of LLA use with high-sensitivity C-reactive protein (hs-CRP) and oral inflammation. DESIGN: Cross-sectional analysis using baseline data from 1300 overweight/obese participants aged 40-65 years, recruited for the ongoing San Juan Overweight Adults Longitudinal Study. Serum hs-CRP was measured by ELISA, gingival/periodontal inflammation was evaluated as bleeding upon probing (BOP), and LLA was self-reported. Separate logistic models were performed for systemic and oral inflammation. RESULTS: In all, 24% participants reported history of dyslipidaemia, of which, 50.3% self-reported LLA use. Sixty percent of the participants had elevated hs-CRP (>3 mg/dl) and 50% had high BOP (defined as at or above the median: 21%). After adjusting for age, gender, smoking, HDL-C, physical activity, diabetes, blood pressure medications, and percent body fat composition, LLA users had significantly lower odds of elevated hs-CRP compared to LLA non-users (OR = 0.58; 95% CI: 0.39-0.85). After adjusting for age, gender, smoking status, educational level, mean plaque index and percent body fat, LLA users had significantly lower odds of high BOP compared to LLA non-users (OR = 0.62; 95% CI: 0.42-0.91). CONCLUSIONS: Lipid-lowering agents may reduce both systemic and oral inflammatory responses.

Potential association between prediabetic conditions and gingival and/or periodontal inflammation.

AIMS/INTRODUCTION: Prediabetic conditions, which include impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), might be associated with chronic gingival and/or periodontal inflammation. However, the occurrence of this oral inflammation in prediabetic conditions is poorly understood. The present study aimed to assess the association between prediabetes and gingival and/or periodontal inflammation. MATERIALS AND METHODS: A total of 94 Puerto Rican men and women aged 40-65 years, who were residents of San Juan, Puerto Rico, and free of diabetes, were included in the study. All participants had at least one tooth site with clinical attachment loss ≥3 mm. Fasting and 2-h plasma glucose were collected. Gingival/periodontal inflammation was assessed by bleeding on gentle probing of the sulcus at six sites per tooth. RESULTS: Participants with the percentage of teeth with bleeding on probing (BOP) equal to or greater than the median were compared with those with the percentage of teeth with BOP less than median. Participants with high BOP tended to present higher IFG (odds ratio [OR] 5.5, 95% confidence interval [CI] 1.2-25.3) and/or prediabetic condition (OR 3.6, 95% CI 1.0-13.2) than those with a low percentage of BOP, adjusting for age, sex, smoking, alcohol consumption, waist circumference and number of missing teeth. Using the continuous form of the outcome, the corresponding adjusted least squares means of percentage of BOP were 26.8 (standard error of the mean [SEM] 2.3) and 43.8 (SEM 6.0) in normal and IFG, respectively (P = 0.01), and 27.0 (SEM 2.4) and 39.0 (SEM 5.3) among healthy and prediabetic individuals, respectively (P = 0.05). CONCLUSION: IFG and/or prediabetes are strongly associated with BOP, a marker of chronic gingival/periodontal inflammation.

Bacterial infection increases periodontal bone loss in diabetic rats through enhanced apoptosis.

Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α-expressing cells and increased apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3-dependent mechanism.

Lipid peroxidation is associated with the severity of periodontal disease and local inflammatory markers in patients with type 2 diabetes.

CONTEXT: Periodontitis is the most common lytic disease of bone and is recognized as a common complication of diabetes. Lipid peroxidation (LPO) is increased in diabetes and may be related to modulation of the inflammatory response. LPO levels in patients with diabetes and periodontal disease have not been evaluated. OBJECTIVE: The aim of this study was to evaluate the levels of LPO and its correlation with periodontal status and inflammatory cytokines in type 2 diabetic and nondiabetic patients. DESIGN AND SETTING: This is a cross-sectional study involving Brazilian patients recruited at the State University of São Paulo. PATIENTS: The sample comprised 120 patients divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetics with dyslipidemia, well-controlled diabetics with dyslipidemia, normoglycemic individuals with dyslipidemia, and healthy individuals. MAIN OUTCOME MEASURES: Blood analyses were carried out for fasting plasma glucose, glycated hemoglobin, and lipid profile. Periodontal examinations were performed, and gingival crevicular fluid was collected. LPO levels were evaluated by measuring oxidized low-density lipoprotein (ELISA) and malondialdehyde (HPLC). Cytokines were evaluated by the multiplex bead technique. RESULTS: LPO evaluated by malondialdehyde in plasma and gingival crevicular fluid was significantly increased in diabetes groups. Significant correlations between LPO markers and periodontal parameters indicate a direct relationship between these levels and the severity of inflammation and secretion of inflammatory cytokines, particularly in diabetic patients. CONCLUSION: These findings suggest an important association for LPO with the severity of the local inflammatory response to bacteria and the susceptibility to periodontal disease in diabetic patients.

Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3-dependent mechanism in experimental periodontitis.

The purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced by Aggregatibacter actinomycetemcomitans infection. Thirty-eight diabetic and 33 normal rats were inoculated with A. actinomycetemcomitans and euthanized at baseline and at 4, 5, and 6 weeks after inoculation. Bone loss and the infiltration of polymorphonuclear leukocytes (PMNs) in gingival epithelium were measured in hematoxylin-eosin-stained sections. The induction of tumor necrosis factor alpha (TNF-α) was evaluated by immunohistochemistry and of apoptotic cells by a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay. After A. actinomycetemcomitans infection, the bone loss in diabetic rats was 1.7-fold and the PMN infiltration 1.6-fold higher than in normoglycemic rats (P < 0.05). The induction of TNF-α was 1.5-fold higher and of apoptotic cells was up to 3-fold higher in diabetic versus normoglycemic rats (P < 0.05). Treatment with a caspase-3 inhibitor significantly blocked noninflammatory cell apoptosis induced by A. actinomycetemcomitans infection in gingival epithelium and connective tissue (P < 0.05). These results provide new insight into how diabetes aggravates A. actinomycetemcomitans-induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection.

A.actinomycetemcomitans-induced periodontal disease promotes systemic and local responses in rat periodontium.

AIM: To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. MATERIAL & METHODS: Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-α in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. RESULTS: An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p < 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p < 0.05). TNF-α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF-α expression in the connective tissue (p < 0.05). PMN recruitment significantly increased after Aa infection (p < 0.05). Aa also increased the number of CD8(+) T cells (p < 0.05), but not CD4(+) T cells or regulatory T cells (Tregs) (p > 0.05). CONCLUSION: Aa infection stimulated a local response that increased numbers of PMNs and TNF-α expression in the junctional epithelium and loss of attachment. Both TNF-α expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-α in the connective tissue, osteoclast numbers and CD8(+) T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction.

Animal models to study host-bacteria interactions involved in periodontitis.

Animal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of are pair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them.

Association between periodontal pathogens and risk of nonfatal myocardial infarction.

BACKGROUND: The direct effect of periodontal pathogens on atherosclerotic plaque development has been suggested as a potential mechanism for the observed association between periodontal disease and coronary heart disease, but few studies have tested this theory. OBJECTIVES: (i) To assess the association of periodontal pathogens in periodontal pockets with the risk of myocardial infarction (MI) and (ii) to assess whether an increase in the number of periodontal bacterial species increases the risk of MI. METHODS: A total of 313 cases and 747 controls, consisting of Caucasian men and women from Western New York, aged 35 to 69 years, were recruited for this study. The presence of microorganisms was assessed by indirect immunofluorescence microscopy, using species-specific polyclonal and monoclonal serodiagnostic reagents. The presence of six periodontal pathogens, Porphyromonas gingivalis (Pg), Tannerella forsythensis (Tf), Prevotella intermedia (Pi), Campylobacter recta (Cr), Fusobacterium nucleatum (Fn), and Eubacterium saburreum (Es), and their co-occurrence (0-6) was compared with the odds of having myocardial infarction. RESULTS: Univariate analyses revealed a higher percentage of the presence of each bacterium in cases compared to controls. In multivariate analyses, only Tf and Pi were statistically associated with an increase in the odds of having MI [Odds ratio OR=1.62; 95% CI (1.18-2.22); and 1.40; 95% (1.02-1.92), respectively] after adjusting for age, gender, education, cholesterol, high blood pressure, diabetes, and total pack-years of cigarette smoking. An increase in the number of different periodontal bacteria in pockets was also found to increase the odds of MI [adjusted OR=1.14; 95% CI (1.03-1.26)]. Participants who had three species or more of periodontal pathogens had about 2-fold increase in odds of having nonfatal MI than those who did not have any type of bacterial species [OR=2.01 (1.31-3.08)]. CONCLUSION: The presence of periodontal pathogens, specifically Tf or Pi, and an increase in total burden of periodontal pathogenic species were both associated with increased odds of having MI. However, further studies are needed to better assess any causal relationship, as well as the biological mechanisms underlying this association.

Periodontal disease and risk of myocardial infarction: the role of gender and smoking.

BACKGROUND: Studies examining the association between periodontal disease and coronary heart disease have shown a consistent but weak to moderate relationship. Limited data have been reported in women and the role of smoking has not been fully clarified. METHODS/RESULTS: A population-based case-control study examining the association between periodontal disease (PD) and acute non-fatal myocardial infarction (MI) was conducted in Erie and Niagara counties in Western New York State. Cases (574) were discharged alive from local hospitals with MI diagnosis. Controls (887) were county residents randomly selected from the NY State Department of Motor Vehicles rolls and Health Care Financing Administration files. Periodontal disease was assessed using clinical attachment loss (CAL). Among men (415 cases), the odds ratio (OR) of the association between mean CAL (mm) and MI, adjusting for the effects of age, body mass index (BMI), physical activity, hypertension, cholesterol, diabetes, and total pack-years of cigarette smoking was 1.34 (1.15-1.57). In women (120 cases), the corresponding OR was 2.08 (1.47-2.94). The estimate of this association among non-smokers, also adjusting for age, gender, BMI, physical activity, hypertension, cholesterol, diabetes, and total pack-years of cigarette smoking, was 1.40 (1.06-1.86), while it was 1.49 (1.26-1.77) among smokers. CONCLUSIONS: This study provides evidence of an association between PD and incident MI in both genders. This association appears to be independent from the possible confounding effect of smoking.